Changes in pharmacokinetics of cisplatin after hepatic resection in rats. 1991

K S Hall, and B Lien, and L Endresen, and A Bergan, and H E Rugstad
Department of Clinical Pharmacology, University of Oslo, Rikshospitalet.

Adjuvant chemotherapy concomitant with hepatic resection has been considered as treatment of patients with hepatocarcinoma. To examine the influence of a partial hepatectomy on the platinum pharmacokinetics, rats were given a single dose of cisplatin (2 mg/kg) prior to 2/3 hepatic resection or sham operation. The partially hepatectomized rats showed a 44% increase in the AUC between 2-48 hr compared with the sham-operated controls. The terminal plasma half-life from 12-48 hr was 21.1 hr for the partially hepatectomized rats and 14.7 hr for the sham-operated animals. Total platinum concentration in liver tissue was 1.3 times that of plasma 20 min after injection. Although cisplatin is considered to be eliminated mainly via renal excretion, our finding may suggest a role for the liver in the elimination of platinum.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D010984 Platinum A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". Platinum Black
D011300 Preoperative Care Care given during the period prior to undergoing surgery when psychological and physical preparations are made according to the special needs of the individual patient. This period spans the time between admission to the hospital to the time the surgery begins. (From Dictionary of Health Services Management, 2d ed) Care, Preoperative,Preoperative Procedure,Preoperative Procedures,Procedure, Preoperative,Procedures, Preoperative
D011915 Rats, Inbred BUF An inbred strain of rat that is used for cancer research, particularly the study of CARCINOGENESIS Rats, Inbred Buffalo,Rats, BUF,BUF Rat,BUF Rat, Inbred,BUF Rats,BUF Rats, Inbred,Buffalo Rats, Inbred,Inbred BUF Rat,Inbred BUF Rats,Inbred Buffalo Rats,Rat, BUF,Rat, Inbred BUF
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D006400 Hematocrit The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value. Erythrocyte Volume, Packed,Packed Red-Cell Volume,Erythrocyte Volumes, Packed,Hematocrits,Packed Erythrocyte Volume,Packed Erythrocyte Volumes,Packed Red Cell Volume,Packed Red-Cell Volumes,Red-Cell Volume, Packed,Red-Cell Volumes, Packed,Volume, Packed Erythrocyte,Volume, Packed Red-Cell,Volumes, Packed Erythrocyte,Volumes, Packed Red-Cell
D006454 Hemoglobins The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Eryhem,Ferrous Hemoglobin,Hemoglobin,Hemoglobin, Ferrous
D006498 Hepatectomy Excision of all or part of the liver. (Dorland, 28th ed) Hepatectomies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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